Opsoclonus Myoclonus Ataxia Family Symposium

April 11, 2015

Conference Agenda:

11:00AM Mike Michaelis, OMSLife Foundation

Welcome and Introductions

11:15AM Donald L. Gilbert MD, MS Movement disorders

12:00PM Dr. Allen DeSena, MD Neuro-immunology

1:00PM Mike Michaelis, The OMSLife Foundation

1:15PM Dr. Brian Weiss, MD Oncology

2:00PM Wendi Lopez, PsyD Behavior, Learning at home and school

3:00PM OMS Caregiver Panel Discussion

Opsoclonus Myoclonus Ataxia Syndrome

Neurology/ Movement Disorder Overview

Donald L. Gilbert MD MS

Disclosure

• None relevant to this talk

• Clinical trials (Tourette Syndrome): Psyadon, Otsuka, AstraZeneca

Story

• 21 month old completely healthy girl

• Walked on time

• Uses hands normally – stacks small toys

• Very social, not yet toilet trained but interested

• Points to objects and body parts

• Follows commands with gesture

• Has over 20 words

Story

• One morning she awoke with a cough and a fever

• Over the next two days she had tremors of her body and poor balance. She was fussy. Parents noted some unusual eye movements

Story

• She presented to small hospital, where she was admitted for a workup

• She underwent blood testing, 2 MRI scans, a 24 hour EEG, and a spinal tap

• All tests were normal

Diagnosis?

“Acute Cerebellar Ataxia”

Story continued

The girl was sent home with her parents to wait for symptoms to

improve

Story continued

The symptoms did not improve

Story continued

• The child’s pediatrician was not sure what to do

• The child was sent to the ER and another MRI was performed, but discharged home again

• The pediatrician referred her for a second opinion

Story continued

• For 4 weeks she continued to get worse

• “Sometimes conditions get worse before they get better”

• She is very fussy, has stopped speaking, is very shaky, cannot or will not walk

• On the morning of her “second opinion” visit she spikes another fever

Story continued

• At the check in at the neurologists office, the medical assistant thinks she is having a seizure she is so shaky

• Her eyes are out of control, bouncing up and down really fast so she can’t maintain eye contact with her parents

• She is so fussy her parents can’t comfort her

Diagnosis?

Acute Cerebellar Ataxia

Opsoclonus Myoclonus (Ataxia) Syndrome

Why is this diagnosis difficult?

Feature/ Symptom Opsoclonus myoclonus

Acute Cerebellar Ataxia

Onset around age two

Yes Yes

Presents with or after illness

Yes Yes

Balance problems Yes Yes

Hand tremors Yes Yes

Eye problems Yes Yes

Category Examples Clinical features, diagnostic essentials

Acute

Toxic Acute ingestion Alcohol, anticonvulsants, antihistamines, benzodiazepines

Toddlers – accidental ingestion; Adolescents – substance abuse. Mental status changes common, urine/serum toxicology screen in Emergency Department may detect unsuspected ingestions.

Inflammatory Acute cerebellar ataxia Symmetric cerebellar findings, gait impairment, truncal ataxia, titubation, nystagmus. Mental status normal. Usually post-infectious. Consider opsoclonus myoclonus ataxia syndrome.

Trauma/Vascular Stroke, vertebrobasilar dissection Consider after neck trauma or if hypercoagulable.

Recurring

Metabolic Many inborn errors of metabolism may occur intermittently Can be triggered by intercurrent illness. Consider if child has preexisting intellectual disabilities, positive family history, consanguinity; or presents with encephalopathy and vomiting.

Migrainous Basilar migraine, benign paroxysmal vertigo

In the young child, headache may not be prominent. Initial episode consider focal pathology and need for imaging.

Episodic Ataxias Episodic Ataxia 1, 2 Bouts of dysarthria, gait ataxia, sometimes with characteristic provoking factors.

Functional Psychogenic / Functional Neurologic Symptom Disorders Gait disturbance or abnormal tremor-like movements which have fluctuating, on-off time course, variable direction, amplitude, and frequency, and otherwise do not conform to usual pattern of disease. Uneconomical gait, excessive sway without falling may be seen.

Subacute

Inflammatory

Acute Disseminated Encephalomyelitis (ADEM)

Mental status changes; and multifocal neurologic deficits. MRI shows multiple discrete lesions involving white and gray matter.

Guillain Barre Syndrome, including Miller Fischer Variant

Oculomotor paresis, bulbar weakness, hyporeflexia, radicular pain. Risk for respiratory/autonomic failure. Note – weakness localizing peripherally may masquerade as ataxia due to problems with limb control and gait. .

Opsoclonus myoclonus ataxia syndrome

Truncal ataxia, multifocal myoclonus, opsoclonus (may be transient), behavioral irritability. Paraneoplastic (neuroblastoma) or post-infectious.

Mass lesions

Posterior fossa neoplasms Headaches, vomiting, papilledema, cranial nerve palsies.

Lots of causes of acute balance problems in children

Spino-cerebellar Ataxia youngest age reported onset in years other features in addition to ataxia MRI Findings Gene Protein Mutation Type

SCA2 0 slow saccades and tracking, peripheral sensory loss Olivoponto-cerebellar atrophy, posterior column degeneration ATXN2 ataxin-2 CAGn

SCA29 0 congenital nonprogressive, nystagmus, motor delays, mild cognitive impairment cerebellar vermis hypotrophy ITPR1 inositol 1,4,5-triphosphate receptor, type 1 various

SCA34 0 nystagmus; early childhood skin lesions: erythrokeratodermia, papulosquamous erythematous plaques; hyperkeratosis, ataxia, hyporeflexia cerebellar atrophy ELOVL4 elongation of very long chain fatty acids-like 4 various

SCA7 1 pigmentary macular degeneration, ophthalmoplegia, spasticity or parkinsonism, sensory loss, dementia olivopontocerebellar atrophy ATXN7 ataxin-7 CAGn

SCA21 1 oculomotor abnormalities, nystagmus, parkinsonism, cognitive impairment, hyporeflexia cerebellar atrophy TMEM 240 transmembrane protein at synapse various

SCA25 1 nystagmus, GI complaints, pes cavus, extensor plantar plus areflexia, sensory neuropathy, cerebellar atrophy 2p locus unknown unknown

SCA5 2 downbeat nystagmus, gaze-evoked nystagmus, facial myokymia, hyperreflexia cerebellar atrophy SPTBN2 beta III spectrin, associated with Glutamate Transporter EAAT4 various

SCA1 3 oculomotor abnormalities, spasticity/hyper-reflexia, EPS, neuropathy olivopontocerebellar atrophy, posterior column degeneration ATXN1 ataxin-1 CAGn

SCA13 4 nystagmus, ataxia, hyperreflexia, developmental delay, intellectual disability cerebellar atrophy KCNC3 voltage gated potassium channel various

SCA14 5 myokymia, ocular movement abnormality, nystagmus, ataxia, hyperreflexia, dementia, depression, attention deficits, decreased vibratory sense cerebellar atrophy PRKCG protein kinase C gamma polypeptide various

SCA28 6 oculomotor abnormalities, ophthalmoparesis, ptosis, rare dystonia/PD, spasticity cerebellar atrophy AFG3L2 ATPase family gene 3-like 2 various

SCA12 8 myokymia, ocular movement abnormality, ataxia, tremor, hyperreflexia, dementia, depression, anxiety, delusions cortical and cerebellar atrophy PPP2R-2B upstream of coding region for brain-specific regulatory subunit of protein phosphorylase PP2A CAGn

SCA15 10 ocular movement abnormalities, nystagmus, ataxia, hyperreflexia, tremor cerebellar atrophy ITPR1 inositol 1,4,5-triphosphate receptor, type 1 various

SCA18/ SMNA 10 nystagmus, muscle atrophy and weakness, ataxia, hypo/areflexia, axonal sensory neuropathy cerebellar atrophy IFRD1 interferon-related developmental regulator gene Non-synonymous variant

SCA27 12 oculomotor abnormalities, nystagmus, pes cavus, intellectual disability, aggression, sensory neuropathy cerebellar atrophy; basal ganglia degeneration FGF14 fibroblast growth factor 14 various

SCA3/MJD 13 parkinsonism, decreased eye movements, loss of reflexes, nystagmus, fasciculations cerebellar atrophy, mild ATXN3 ataxin-3 CAGn

SCA19 15 nystagmus, ataxia, hypo or hyperreflexia, tremor, rigidity, myoclonus, cognitive impairment, reduced vibratory sense cerebellar atrophy KCND3 voltage gated potassium channel, SHAL-related subfamily, member 3 various

SCA4 19 axonal sensory neuropathy cerebellar atrophy BEAN brain-expressed, associated with NEDD4 Insertion within intron

SCA10 19 seizures, ocular movement abnormalities, mood disorders, polyneuropathy cerebellar atrophy ATXN10 ataxin-10 ATTCTn

SCA17 19 Ocular movement abnormalities, ataxia, parkinsonism, dystonia, chorea, dementia, seizures, depression, hallucinations, aggression, frontal release - HD like or PD like cerebral and cerebellar atrophy, gliosis in stratium, medial thalamic nuclei, inferior olives TBP TATA box-binding protein CAGn

SCA20 19 dysarthria, dysphonia, nystagmus, tremor, ataxia Dentate nucleus calcification 11q12.2-11q12.3 unknown contiguous duplication (contains >11 genes)

SCA6 20 nystagmus, dysarthria, vibratory and proprioceptive loss; some hemiplegic migraine cerebellar atrophy CACNA-1A Calcium Channel, L Type, Alpha-1A subunit CAGn

SCA8 20 spastic dysarthria, spasticity, vibratory loss cerebellar atrophy ATXN8; ATXN8-OS ataxin-8 CAGn; CTGn

SCA11 20 ataxia, dysarthria, hyperreflexia cerebellar atrophy TTBK2 tau tubulin kinase-2 indel in coding regions

SCA26 20 oculomotor abnormalities, nystagmus, ataxia cerebellar atrophy EEF2 elongation factor 2 various

SCA35 20 oculomotor abnormalities, torticollis, ataxia, hyperreflexia cerebellar atrophy TGM6 transglutaminase 6 various

SCA36 29 hearing loss, nystagmus, tongue fasciculations/atrophy, skeletal muscle atrophy, denervation, ataxia, hyperrelexia, cerebellar atrophy NOP56 nucleolar ribonucleoprotein complex component of box C/D GGCCTGn repeat insertion in intron

SCA32 30 ataxia, azoospermia cerebellar atrophy 7q32-q33 unknown unknown

SCA37 38 oculomotor abnormalities (vertical, horizontal), nystagmus, ataxia, cerebellar atrophy 1p32 unknown unknown

SCA23 40 oculomotor abnormalities, ataxia, tremor, mild cognitive decline, axonal polyneuro-pathy cerebellar atrophy PDYN Prodynorphin various

SCA30 45 ataxia, dysarthria, hyperreflexia cerebellar atrophy 4q34.3-q35.1 unknown unknown

SCA31 45 late sensorineural hearing loss, nystagmus, ataxia cerebellar atrophy BEAN brain-expressed, associated with NEDD4 TGGAAn repeat insertion in intron

Many Genetic Ataxias!

Why is this diagnosis difficult? Overlap

Feature/ Symptom Opsoclonus myoclonus

Acute Cerebellar Ataxia

Onset around age two

Yes Yes

Presents with or after illness

Yes Yes

Balance problems Yes Yes

Hand tremors Yes Yes

Eye problems Yes Yes

Categories of disease causing myoclonus in children Etiological Category

Clinical Features

Physiologic

Myoclonus occurs in certain settings in healthy persons. Examples include sleep (hypnic) jerks, hiccoughs, and benign infantile myoclonus with feeding. 15

Benign, developmental Myoclonus as a transient symptom during otherwise normal development. Examples include benign neonatal myoclonus and myoclonus of early infancy. See also chapter 6.

Startle syndromes Quick, involuntary, stimulus-evoked reflex movements. An exaggerated startle response that may be further subdivided into hereditary, symptomatic, startle epilepsy, and neuropsychiatric startle syndromes (Latah syndrome, jumping Frenchman of Maine, anxiety-induced startle).16

Primary myoclonus disorders Myoclonus occurs as the primary symptom. The cardinal example is essential myoclonus. 17,18

Epileptic

Myoclonus is associated with clinical seizures and/or epileptiform discharges on EEG, supportive of a cortical origin.

Primary epileptic myoclonus disorders Myoclonus as a seizure type or fragment, or myoclonus as a symptom in addition to seizures in an epilepsy syndrome without encephalopathy.19,20

Progressive myoclonic epilepsies and progressive encephalopathies with myoclonus

Myoclonus occurs as part of a multi-symptom, progressive neurologic disease.

Secondary myoclonus disorders Myoclonus occurs secondary to some other identifiable, non-genetic cause or process. Examples include autoimmune diseases, infections/encephalitides, hypoxic ischemic injury (Lance Adams myoclonus), toxins, metabolic derangements such as uremia, acidosis. Also, secondary to medications, e.g. myoclonus triggered by the use of focal antiepileptic medications in patients with generalized epilepsies.21-23 See Chapter also 22.

Psychogenic/ Functional Pseudomyoclonus as a symptom of a Functional Neurological Symptom Disorder/Psychogenic Movement Disorder.24-26 See also Chapter 23.

Disease Gene (locus)/ Protein Inheritance Clinical Features Age of onset

Primary myoclonus

Hereditary Geniospasm166 possible linkage to 9q13-q21 AD chin myoclonus/ tremor childhood

Myoclonus Dystonia Syndrome : DYT11, DYT 1556,61,167-169 SGCE; epsilon sarcoglycan; DRD2 Dopamine receptor 2 AD bilateral myoclonus, tremor, dystonia, torticollis, depression, anxiety, Obsessive Compulsive disorder

5-15 years

Epileptic myoclonus without encephalopathy

Juvenile Absence Epilepsy EJA1170 EFHC2; EF-HAND Domain (C-terminal)-containing protein 2 AD Absence seizures, generalized tonic clonic seizures, myoclonic seizures childhood, around puberty

Juvenile Myoclonic Epilepsy EJM171-178 GABRA1 and GABRD GABA receptors; CACNB4 Calcium Channels; CLCN2 Chloride Channels AD Morning myoclonic jerks, absence and GTC seizures childhood and adolescence

Myoclonus plus encephalopathy

Amish Infantile Epilepsy Syndrome179 SIAT9; sialytransferase-9 AR failure to thrive, visual loss, startle myoclonus, epilepsy, no development, early death infancy

Aromatic L-Amino Acid Decarboxylase Deficiency180 DDC; dopa-decarboxylase AR oculogyric crises, opisthotonus, dystonia, myoclonus, hyperreflexia, chorea, irritability infancy

Combined Saposin Deficiency181,182 PSAP; prosaposin AR myoclonus, dyskinesias, seizures, organomegaly, respiratory failure Infancy

Dentatorubral-pallidoluysian Atrophy (DRPLA)183 ATN1expanded trinucleotide repeat; atrophin 1 AD seizures, ataxia, choreoathetosis, myoclonus, dementia usually 30's, can occur in childhood

Gaucher Disease IIIA184 GBA; Acid beta-glucocerebrosidase AR Myoclonus, spastic paraparesis, dementia, seizures, ataxia, organomegaly, abnormal saccades, short stature

early to late childhood

Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome185,186 SCLC25A15; solute carrier family 25 member 15 AR Myoclonic epilepsy, dementia, pyramidal signs and spasticity, neuropathy, episodic vomiting Infancy

Mitochondrial complex II deficiency187 SDHAF1; succinate dehydrogenase complex AR short stature, cardiomyopathy, leukoencephalopathy, spongiform encephalopmyopathy, ataxia, myoclonus, seizures

Childhood

Myoclonic Epilepsy associated with Ragged Red Fibers MERRF188,189 Multiple mitochondrial transfer RNA genes, MTTK, MTTL1, MTTH, MTTS1, MTTS2, MTTF Mitochondrial myoclonus, epilepsy, ataxia, spasticity, weakness, deafness childhood or adulthood

Neuronal Ceroid Lipofuscinosis 1190 PPT1; palmitoyl-protein thioesterase-1 AR Progressive visual loss, dementia, myoclonus, ataxia, epilepsy, early death; variable - later onset with psychiatric symptoms

Early childhood; late childhood or adult

Neuronal Ceroid Lipofuscinosis 2191 TPP1; tripeptidyl peptidase 1 AR Progressive visual loss, dementia, myoclonus, ataxia, epilepsy, early death Early childhood

Neuronal Ceroid Lipofuscinosis 3192 CLN3, battenin AR Progressive visual loss, dementia, myoclonus, ataxia, epilepsy, early death Childhood

Neuronal Ceroid Lipofuscinosis 5193 CLN5 AR Progressive visual loss, dementia, myoclonus, ataxia, epilepsy, early death Childhood

Neuronal Ceroid Lipofuscinosis 8194 CLN8 AR Dementia, myoclonus, epilepsy, ataxia, atrophy early childhood

Progressive Myoclonic Ataxias / Ramsay Hunt Syndrome195 None- the literature on this syndrome probably represents a collection of diagnoses, including some that now could have molecular diagnosis

AD/ other Myoclonus, ataxia, tremor, GTCs, degeneration of dentate nucleus, globus pallidus, mitochondrial disease findings

Childhood

Progressive Neuronal Degeneration of Childhood with Liver Disease (Alpers Huttenlocher)196 POLG1 DNA mitochondrial polymerase gamma AR failure to thrive, visual loss, myoclonus, epilepsy, ataxia, early death Infancy

Pyridoxine 5-Prime Phosphate Oxidase deficiency197 PNPO Pyridoxine Phosphate Oxidase AR myoclonus, neonatal epileptic encephalopathy, partial response to pyridoxine, seizure response to pyridoxal phosphate

infancy, usually preterm delivery

Rett Syndrome in Males198,199 MECP2 X linked Severe encephalopathy, myoclonus, rigidity, death in 2 years Infancy

Schindler Disease, infantile type200 NAGA; alpha-N-acetylgalactosaminidase AR visual loss, dementia, spasticity, myoclonus, brain atrophy early childhood

Sialidosis I and II159 NEU1; Neuraminidase AR Storage phenotype - coarse facies retardation, coarse geatures features, asdlf can be early childhood

Spinocerebellar ataxia type 19201 Linkage 1p21-q23 AD ataxia, myoclonus, tremor usually adult, some child

Spinocerebellar ataxia type 2202 ATXN2 expanded trinucleotide repeat; ataxin 2 AD Dementia, myoclonus, epilepsy, ataxia, atrophy, abnormal eye movements usually adult, some infants

Progressive myoclonic epilepsy

Myoclonic Epilepsy - Unverricht and Lundborg EPM1A 203 CSTB; Cystatin B/Stefin B AR Myoclonus, ataxia, GTCs, Absence Seizures, Dysarthria, mental deterioration Childhood

Epilepsy, Progressive Myoclonic EPM 1B204 PRICKLE1; Rest-interacting Lim Domain Protein AR Upward gaze palsy, Motor delays with ataxia early, seizures later childhood Early childhood

Myoclonic Epilepsy – Lafora EPM2A147 EPM2A; Laforin AR myoclonus, epilepsy, apraxia, dementia, visual loss, psychosis late childhood

Myoclonic Epilepsy – Lafora EPM2B148 NHLRC1; malin AR myoclonus, epilepsy, apraxia, dementia, visual loss, psychosis late childhood

Action Myoclonus Renal Failure Syndrome205 SCARB2 (Scavenger Receptor, Class B, member 2) AR Progressive action myoclonus, finger tremor, ataxia, GTCs, nephropathy/renal failure late teens

Many Genetic causes of

Myoclonus

Story reprise

• The girl developed tremor and poor balance

Ataxia

• Problems in the timing of motor movements

• Inability to coordinate sequential parts of movement so that they are smooth and effective

The story reprise

• On more careful observation – she had many quick jerky movements of her body, her neck, and her limbs

Myoclonus

• Muscle jerks

• If they occur in the trunk muscles this can throw you off balance

• If they occur in the leg muscles they can also throw you of balance

• If they are small and frequent you can look like you have ataxia

The story

• Her eye movement problems were obvious at the second opinion – but may not have been so obvious every time doctors saw her

Eye movements

• Normal movements

• Fix your gaze on a target of interest

• Rapidly move your eyes to a new target

Cerebellar diseases and the eyes • Nystagmus – poor gaze fixation. The eyes

drift, the brain keeps trying to get back to the target so you have repeated eye drift/jerk drift/jerk movements that are very quick and fluttery

• Opsoclonus – brain activity controlling quick movements to targets is abnormal, so the quick movements happen in many directions very quickly – burst of quick eye movements

• Estimate of incidence: less than one case per million children per year

• Probably fewer than 100 cases per year

3 cellular layers in cerebellum

Granular

Molecular

Purkinje

Apps R, Garwicz M. Nature Reviews Neuroscience 2005

Traditionally the cerebellum was thought to primarily control

movement coordination

But the cerebellum is also important for:

• Impulse control

• Emotional regulation

• Social understanding

So the key to diagnosing OMAS is:

• The doctor has to recognize it

• Doctors, child neurologists especially, need to be well trained

Before discussing the immune system and neuroblastoma

Two other topics:

Types of Doctors

Navigating Web Information

Who is my doctor?

Primary Care Physicians

• The Go-To, front line doctors: Stay Here

• Pediatricians, Family Practitioners, affiliated

NPs

• Diagnose common problems like ADHD

(Am Acad Pediatrics: ADHD Toolkit)

Adult Neurologists

• Not ideal

• Note – in many communities the most accessible neurologist for a child to see is an adult neurologist

Child Neurologists

• Goal 1: Diagnosis. Ideally Specific. Should have a biological (cellular, genetic, molecular) basis, based on careful history and physical examination as well as from diagnostic testing: blood/urine/spinal fluid; MRI, Neurophysiology/EEG

• Goal 2: Rational, Evidence Based Intervention

• Often work in teams. We do not see ourselves as “pediatricians first” but we are still full medical doctors

• Prescribe medications

• Typically receive 12 months of adult neurology training

Child Neurologists

• Perspective: Children are not small adults

• We are actively involved on the genetics frontier

• We may or may not understand much immunology

• We understand that the diseases we see affect education but our training does not necessarily emphasize this in helpful ways

• The majority of us work in academic centers, not in private practice or in more rural areas

Child Neurologists

• Really rare diseases

– There are a lot of really rare diseases we see

– Some of these are partly managed in a few

specialized centers around the country

Child Neurologists

• Most of what we treat is not curable

• There are increasing numbers of treatments

but there are still chronic conditions for

which we can provide little directly beneficial

treatment

Neurosurgeons

• Goal 1: discern when and when not to operate

• Goal 2: Fix Problems

• Pediatric medicine training: minimal

Pediatric Physiatrists “PM&R”

• Goal: rehabilitation and adaptation to

diseases and injuries of the brain

• Diagnosis has already been made, typically

• Multi-disciplinary – work with physical,

occupational, speech therapists to improve

function, independence, well being

Developmental Pediatricians

• Goal: manage the medical and psychosocial aspects of children’s and adolescents’ developmental and behavioral problems

• Emphasis more on disordered or atypical development, less on disease or brain injury

• Like physiatrists work collaboratively with therapy teams

• Very interested in schools

Psychiatrists

• Medication Treatment

• Work with a “med check” model for

follow ups

• Interest/skill in therapy variable

• Can do a one-year fellowship in child

psychiatry

Child Psychiatrists

• Medication Treatment

• Work with a “med check” model for follow ups

• May take particular interest in neurological

condition that has high psychiatric comorbidity

• Interest/skill in therapy variable

• Badly Outnumbered because they are treating

society, not just disease

Psychologists

• Work with behavior as

environmentally modifiable

through evidence based

techniques

• Work on problem solving,

parenting techniques

The Way Forward

Navigating information successfully on

your own

Tools for keeping

yourself informed

about new medical

information

“Baloney”

Half-truths

and wishful

thinking

“Possibly

true”

Probably

True

TRUE

(Certainty)

Information Metric v.1

Sources – PRETTY STRONG

• Major Medical Journals: NEJM, JAMA, LANCET,

• Major Specialty Journals: NEUROLOGY

• Medical Society Published, Evidence-Based Practice Guidelines and Patient Pages (examples in this talk)

• Advocacy organization websites with reputable medical advisory boards

• Hospitals with patient health topic pages, e.g. Cincinnati Children’s, Mayo Clinic

• National Institutes of Health / National Library of Medicine

• Accredited Continuing Education

.org

.edu

.gov

Websites you can trust

usually end with

Sources – beware of baloney

• Top Internet hits from

your search

• Some Psychiatry Journals

• Journals your doctor has

never heard of

• Network TV shows

• Lectures/Webinars/Blogs

online by sincere but wacky

doctors who tell lots of

anecdotes

• Websites by unregulated

purveyors of nutritional

products and non-validated

therapies that you have to

pay directly for

How do we know if a treatment

really works?

• Our best estimate of whether something

really works is from Randomized Controlled

Clinical Trials – look for this when you are on

the internet seeking new treatments

Story continues… • Four years after her neuroblastoma was

resected she is off all medication

• She runs but is clumsy, speaks less often and less clearly than her peers

• She attends school, has an IEP

• She has no more opsoclonus or myoclonus

• She is a bit feisty, but her behavior is OK

• She is making cognitive gains, slowly

Will she catch up?

Questions?

Donald L. Gilbert MD MS

Professor of Pediatrics and Neurology

Director, Movement Disorder and Tourette Syndrome Program

Donald.gilbert@cchmc.org